A Combined Theoretical and Experimental Study of Efficient and Fast Titanocene-Catalyzed3-exoCyclizations

Abstract

The mechanism of titanocene mediated 3-exo cyclizations was investigated by a combined theoretical and experimental study. A gradient corrected density functional theory (DFT) method has been scaled against titanocene dichloride, the parent butenyl radical, and in bond dissociation energy (BDE) calculations. The BP86 method using density fitting, and a basis set of triple-zeta quality emerged as a highly reliable tool for studying titanocene mediated radical reactions. The computational results revealed important kinetic and thermodynamic features of cyclopropane formation. Surprisingly, the beta-titanoxy radicals, the first intermediates of our investigations, were demonstrated to possess essentially the same thermodynamic stabilization as the corresponding alkyl radicals by comparison of the calculated BDEs. In contrast to suggestions for samarium mediated reactions, the cyclization was shown to be thermodynamically favorable in agreement with earlier kinetic studies. It was established that stereoselectivity of the cyclization is governed by the stability of the intermediates and thus the trans disubstituted products are formed preferentially. The observed ratios of products are in good to excellent agreement with the DFT results. By a combination of computational and experimental results, it was also shown that for the completion of the overall cyclopropane formation the efficiency of the trapping of the cyclopropylcarbinyl radicals is decisive.

The Nugent Reagent: A Formidable Tool in Contemporary Radical and Organometallic Chemistry

“…These protocols have been used by different authors to develop new methods for cyclisation of unsaturated epoxides. Specifically, epoxy alkenes and epoxy alkynes,14,21 epoxy aldehydes,22 epoxy nitriles,22 epoxy ketones,22 epoxy esters23 and epoxyamides23 have been used as substrates in Cp 2 TiCl‐mediated cyclisation reactions. In all these cases, the proposed mechanism for cyclisation involved alkytitanium(III) species, formed by the trapping of the carbon‐centred radical resulting from the cyclisation step by a second molecule of Cp 2 TiCl (Scheme ).…”

Similarities and differences of epoxide, aldehyde and peroxide initiators for Cp2TiCl-catalyzed styrene living radical polymerizations

“…The epoxide RRO proceeds with the formation of a mixture of reactive, constitutionally isomeric primary and secondary b-titanoxy radicals (Scheme 1, Eqs. (2) and (3)), where typically the secondary radical is favored, but both have the same thermodynamic stabilization as the corresponding alkyl radicals [29]. Similarly, aldehydes form reactive a-titanoxy radicals which also add readily to conventional monomers such as (meth)acrylates [21] and styrene [24].…”

Eine wertvolle Ergänzung zum Portfolio der Cycloadditionsreaktionen

“…Als eine mögliche Alternative könnte das Cu II /Enolatradikal 11 entweder aus 7 oder 8 hervorgehen. Die 3 ‐exo ‐Ringschlüsse von 11 wären wegen der großen Benzyl‐Stabilisierung in den ringgeschlossenen Radikalen 12 äußerst vorteilhaft . Danach würde eine Eliminierung von Cu I die Cyclotrimerisierung vervollständigen.…”